Semaglutide tied to significant weight loss when added to intensive behavioral therapy
PLAINSBORO, N.J. -Researchers have found in a new phase 3a trial that Semaglutide 2.4 mg injection demonstrated significant weight loss versus placebo when added to intensive behavioral therapy.
The investigational drug semaglutide 2.4 mg once-weekly subcutaneous (sc) as an adjunct to intensive behavioral therapy (IBT) demonstrated significantly more body weight loss compared to placebo plus IBT.i The STEP 3 phase 3a trial investigated the efficacy and safety of once-weekly semaglutide 2.4 mg after 68 weeks of treatment compared with placebo both as adjunct to IBTi, which consisted of 30 counselling sessions with a registered dietitian over 68 weeks, plus a reduced-calorie diet and increased physical activity. Trial participants were adults with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/ m2) with at least one weight-related comorbidity and without type 2 diabetes (HbA1c <6.5%). An oral presentation of the new data was given today at the ObesityWeek 2020 interactive congress.1
Two distinct statistical approaches to evaluating the effects of semaglutide 2.4 mg were used in the STEP 3 trial: a primary statistical approach that assessed the treatment effect regardless of adherence or use of other anti-obesity therapies, and a secondary statistical approach that evaluated the treatment effect if all participants in the trial adhered to the randomized treatment and did not initiate any other treatment methods.
Based on the primary statistical approach, people treated with once-weekly semaglutide 2.4 mg in addition to IBT lost an average of 16.0% of their body weight from baseline, compared with 5.7% for those who received placebo plus IBT (estimated treatment difference: -10.3 [95% confidence interval: -12.0, -8.6]; p<0.0001). Furthermore, more people treated with semaglutide 2.4 mg plus IBT lost greater than or equal to 5% of their body weight compared to placebo plus IBT (87% vs 48%, respectively).
"Given the multiple weight-loss related challenges faced by people with obesity, patients and practitioners alike need additional medical therapies to support lifestyle interventions, such as IBT, which is a highly intensive weight loss approach," said Professor Tom Wadden, lead investigator and Professor of Psychology in Psychiatry at the Perelman School of Medicine at the University of Pennsylvania. "I'm encouraged to see the significant additional weight loss and improvements in certain cardiometabolic disease risk factors achieved with semaglutide 2.4 mg when added to IBT."
A weight loss of greater than or equal to 10%, 15% and 20% was achieved by 75%, 56% and 36% of those treated with semaglutide 2.4 mg plus IBT respectively, compared to 27%, 13% and 4% of those treated with placebo plus IBT.1 In this trial, semaglutide 2.4 mg plus IBT also demonstrated greater improvements in cardiometabolic risk factors, including waist circumference (-14.6 vs. -6.3 cm) and systolic blood pressure (-5.6 vs. -1.6 mmHg), compared to placebo plus IBT.1
When evaluating the effects of treatment based on the secondary statistical approach, people treated with semaglutide 2.4 mg plus IBT achieved an average weight loss of 17.6%, compared to 5.0% with placebo plus IBT. Additionally, 90% of those who received semaglutide 2.4 mg plus IBT achieved a weight loss of 5% or more after 68 weeks, compared to 50% with placebo plus IBT.1
"Obesity can have a direct impact on health and is linked to many weight-related diseases. There is an unmet medical need to develop treatment options to help people lose weight and keep it off," said Mads Krogsgaard Thomsen, executive vice president and chief scientific officer of Novo Nordisk. "We are delighted with the first full phase 3 results from the STEP trial program, demonstrating that the addition of semaglutide 2.4 mg to IBT can almost triple the magnitude of weight loss achieved with IBT alone, making semaglutide 2.4 mg a meaningful potential future treatment option for people with obesity."
The proportion of participants reporting adverse events was similar in the semaglutide 2.4 mg and placebo groups (95.8% and 96.1%, respectively). The most common adverse events among people treated with semaglutide 2.4 mg were gastrointestinal events (nausea, vomiting, diarrhea and constipation), reported by 82.8% of participants in the semaglutide 2.4 mg group and 63.2% in the placebo group.1 Serious adverse events were reported in 9.1% and 2.9% of participants in the semaglutide 2.4 mg and placebo groups, respectively. The higher rate for semaglutide 2.4 mg was driven by more gallbladder-related serious events and single events unrelated to the treatment.